New measures of cardiovascular dysfunction in people with HIV pose new questions

Gus Cairns, Michael Carter
Published: 21 July 2009

Two studies using new methods to detect changes in arteries that could give rise to cardiovascular disease have generated differing results.

In one, a study using a sensitive ultrasound test found that long-term HIV infection was independently associated in men with an impairment of the artery’s ability to expand, with higher systolic blood pressure as the result. However, this impairment was only seen in men who had had HIV for more than 15 years.

In the other study, researchers found an apparent effect on heart function in patients who had only been on antiretroviral therapy for a month. They used a sophisticated series of PET and CT scans to map coronary perfusion – blood flow through the coronary arteries and into the heart muscle. They found there was a 31% reduction in coronary blood flow in patients taking HIV therapy when subjected to maximum cardiac stress.

In the first study, 115 HIV-positive men from the Multicenter AIDS Cohort Study (MACS) in the SA, the world’s longest-standing cohort study, were enrolled between 2004 and 2006 into a substudy investigating hardening of the arteries. Arterial function in the men was compared with that of 325 HIV-negative men. Nearly half (56) of the HIV-positive men had been diagnosed for more than 15 years, and 91% were taking antiretroviral therapy.

The men’s mean age was 52 years, 74% were Caucasian and 19% were classified as obese (having a body mass index (BMI) above 30 kg/m2).

The men’s carotid arteries (the large arteries carrying blood up to the brain) were imaged using a sensitive ultrasound technique and their distensibility calculated. This is the ratio of arterial diameter at systole (maximum blood pressure, detectable as the pulse) to arterial diameter at diastole (minimum blood pressure).

They then performed an analysis to see what factors were associated with hardening of the arteries. They took into consideration factors associated with a risk of heart disease (age, race, smoking, family history, diabetes, cholesterol and body mass index) as well as HIV-related factors (duration of HIV infection, CD4 cell count, viral load, use of antiretroviral drugs).

Older age, higher systolic blood pressure and HIV infection for over 15 years were all independently associated (p < 0.05) with hardening of the carotid artery. Arterial distensibility decreased by 13.4%, compared with HIV-negative men, in men who had lived with HIV for more than 15 years.

In comparison, ageing ten years and a 10 millimetres of mercury increase in systolic blood pressure were both associated with a decrease in distensibility of 11.5%. These factors were independently associated with arterial hardening and did not cause each other. No other demographic or health characteristic was associated with arterial hardening, though diabetes was associated with a non-significant distendibility decrease of 8%.

Investigator Eric Seaberg commented that there was a “very, very pronounced threshold effect” in his findings; there was no association at all between HIV diagnosis and arterial hardening in men who had been diagnosed for less than 13 to 14 years.

In questions after the presentation, Seaberg commented that there appeared to be no association with antiretroviral therapy as the same associations were observed in men not taking therapy, though as this numbered only ten men it was not statistically significant.

He commented that it was impossible to tell whether his findings were directly associated with length of HIV infection or whether some other aspect in the medical history of a fairly select group of long-term HIV survivors from the pre-HAART era had caused the increased rate of arterial stiffness.

In the second study, Ulrik Kristoffersen of Copenhagen University monitored coronary artery perfusion in eleven patients starting antiretroviral therapy for the first time.

The patients (also all men) were given coronary perfusion tests before they started antiretroviral therapy. They then started on tenofovir/FTC/efavirenz (nine patients), AZT/3TC/efavirenz or AZT/3TC/raltegravir.

Coronary perfusion was then tested again five weeks after the start of therapy. Kristofferson’s team measured perfusion at rest, with the patient’s foot in a bowl of iced water, which simulates sympathetic nervous system stress, and then after giving them a dose of dipyridamol, a drug that dilates the arteries and mimics intense exercise.

After antiretroviral therapy was started, coronary perfusion was the same in patients at rest and subject to sympathetic stress, but was significantly decreased, by 31%, in patients given a dose of dipyridamol (p = 0.021), representing a decrease from 2.6 to 1.7 ml/g/min.

During questions, Kristofferson commented that it was unusual to see rapid changes in coronary blood flow of this degree a month apart. He commented that his technique “could be a powerful tool for studies of the pathophysiology of ART-associated changes in cardiovascular risk.” He was unable to speculate whether the changes seen were short-term changes associated with ARV initiation, permanent ones, or would accumulate over time.

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